Insect Immunity

Mon, 11/03/2008 - 16:47

The sequencing of the Aedes aegypti (Nene et al, 2007) genome, and the availability of the Anopheles gambiae genome (Holt et al, 2002) provided the first opportunity to undertake a detailed comparative genomic analysis between two mosquito species, both vectors of devastating human diseases.

Anopheles is primarily of concern as a vector of the human Malaria parasite, while Aedes transmits Dengue viruses. These mosquitoes diverged ca. 150MYA, and the mosquito lineage split from that of the fruitfly, Drosophila melanogaster, ca. 250MYA. The Aedes immunity project involves a detailed comparison of the immune-related gene repertoires of these three insect species, with reference to other sequenced insect genomes. The project was carried out in conjunction with the Laboratory of Insect Immunogenomics at Imperial College, London.

Predicted genes from all species were classified into orthologous groups and larger clusters of related proteins through all-against-all sequence comparisons. The InterProScan analysis further defined sets of related proteins through the identification of domains which infer characteristic activities or defining protein structural features.

Lists of known immune-related genes from the fruitfly and Anopheles were used as seeds to then identify the full sets of putative immunity genes across all the insect species included in the study.

The results of the initial analysis were made available to experts from the field of insect immunity who confirmed, rejected, or refined the gene family assignments and predicted gene models. This produced manually curated sets of proteins for each of the known immune-related gene families and pathways for the principal insect species.

These were then subjected to a robust evolutionary analysis to identify genes or protein domains which are under similar evolutionary pressures and thereby indicate conserved functions. The analysis also defined orthologous and paralogous relationships to describe in detail the patterns observed in each family.

The full datasets are organised into a web-accessible resource: Immunodb which includes the initial analysis across 12 insect species as well as the refined data, and the evolutionary analyses for the three main species.

The initial release of Immunodb has been archived and replaced with a new, updated version including data on additional immune-related gene families and more insect species.

Mosquitoes are vectors of parasitic and viral diseases of immense importance for public health.
The genome sequence of the yellow fever and Dengue vector, Aedes aegypti (Aa), has enabled a
comparative phylogenomic analysis of the insect immune repertoire: in Aa, the malaria vector
Anopheles gambiae (Ag) and the fruitfly Drosophila melanogaster (Dm). Analysis of immune
signaling pathways and response modules reveals both conservative and rapidly evolving features
associated with different functional gene categories and particular aspects of immune reactions.
These dynamics reflect in part continuous readjustment between accommodation and rejection of
pathogens and suggest how innate immunity may have evolved.